Objective:To investigate the safety of tocilizumab (TCZ) in the treatment of children with systemic juvenile idiopathic arthritis (sJIA).Methods:Data of children aged 2 to 18 years with the diagnosis of sJIA and treated with TCZ from June 1, 2017 to June 30, 2022 at our hospital were retrospectively collected. The clinical medication characteristics, incidence, severity and outcome of adverse drug reactions (ADR) were statistically analyzed. Univariate and multivariate analysis were used to analyze the risk factors of TCZ-induced ADR. Univariate comparison between groups were compared to the measured data followed by t test for normal distribution, and the counting data were paired with Chi-square test. Binary logistic regression analysis was used for multivariate analysis. Results:A total of 83 eligible children were enrolled. The age at TCZ initiation was (8.5±3.7) years old. Most of the children received oral glucocorticoid (86.8%) and/or methotrexate (72.3%) prior to TCZ treatment. The mean time of TCZ duration was (1.2±0.9) years, the total TCZ exposure was 92.70 patient years. Fifty-five (66.3%) children reported 123 ADR, with a rate of 132.69/100 patient years. Forty-two (50.6%) children reported 103 general ADR, with a rate of 111.11/100 patient years. Eighteen (21.7%) children reported 20 serious ADR, with a rate of 21.57/100 patient years. The results of univariate analysis showed that the dosage of glucocorticoid in ADR group was higher than that in non-ADR group [(0.76±0.50) mg·kg -1·d -1vs. (0.52±0.41) mg·kg -1·d -1, t=2.27, P=0.026], and the difference was statistically significant. However, there were no significant differences in gender [(male 23, female 32) cases vs. (male 9, female 19) cases, χ2=0.73, P=0.392], age at TCZ initiation [(8.5±3.8) years old vs. (9.0±3.1) years old, t=-0.65, P=0.516], duration of TCZ treatment [(1.24±1.00) years vs. (1.05±0.90) years, t=0.87, P=0.385], methotrexate doses weekly [(8.0±5.2) mg/m 2vs. (7.6±5.1) mg/m 2, t=0.39, P=0.696], and history of drug or food allergy (11 cases vs. 5 cases, χ2=0.06, P=0.815) between the two groups. The results of binary logistic regression analysis showed that the combined use of oral glucocorticoids was an independent risk factor for TCZ-induced ADR [ OR (95% CI) =3.05 (1.11, 8.36), P=0.030]. The risk of ADR was 3.05 times higher in the combined daily dose of glucocorticoids ≥0.76 mg/kg prednisone equivalent than that of < 0.76 mg/kg. Common general ADR to TCZ include infections (38.83/100 patient years) and abnormalities in laboratory parameters (37.76/100 patient years) such as elevated glutamic-pyrupiane transaminase (18.34/100 patient years), dyslipidemia (12.94/100 patient years), and hemocytopenia (5.39/100 patient years). The serious ADR included serious infection (9.71/100 patient years) and serious infusion reaction(7.55/100 patient years). All ADR were improved after drug withdrawal or symptomatic treatment, and no deaths occurred. Conclusion:TCZ has a good safety profile in the treatment of sJIA. Serious infections and severe infusion reactions often lead to discontinuation of the drug. The combination of glucocorticoids≥0.76 mg/kg prednisone equivalent is an independent risk factor for TCZ-induced ADR. Monitoring should be strengthened during the application of TCZ, and ADR should be detected and treated as early as possible to reduce the risk of medication related adverse reactions.

To analyze the biological characteristics of Pasteurella multocida in bovine respiratory tract and its prevalence in large-scale cattle farms,bacterial isolation,culture,and morphological observation were conducted on the lungs and liver samples of dead cows suffering from respiratory diseases in Hohhot,Inner Mongolia.The isolated strains were studied through biochemical testing,16S rRNA gene sequencing,specific primer PCR identification,capsule serotyping,pathogenicity testing,virulence gene testing,drug sensitivity testing,and drug resistance gene detection methods.The results showed that six strains of Pasteurella multocida serotype A were isolated and identi-fied from the lungs of diseased and dead cows.After sequencing the 16S rRNA sequence of the bac-teria,it was found that the six strains of Pasteurella multocida had the closest genetic relationship with the Chongqing isolate CQ2(CP033599.1).The results of mouse pathogenicity test and viru-lence gene detection showed that all isolates were pathogenic and carried at least 16 or more related virulence genes such as exbB,nanB,sodC,oma 87,etc.,but no hsf1 and toxA were detected.The results of drug sensitivity tests and resistance gene detection showed that the isolated strains were sensitive to different degrees of antibiotics such as ciprofloxacin,ofloxacin,and cefotaxime.They were resistant to streptomycin,clindamycin,and lincomycin,and resistance genes of str A,strB,and tet(H)were detected.The results indicate that there is a certain correlation between the pathoge-nicity and virulence genes,drug resistance phenotype,and drug resistance genes of Pasteurellamultocida type A in cattle.It is recommended to use quinolones(such as ciprofloxacin)and cepha-losporins(such as cefotaxime)antibacterial drugs in clinical practice,which can provide scientific basis and prevention and control plans for the prevention and treatment of respiratory diseases caused by Pasteurella multocida in cattle farms,and lay a foundation for the epidemiological mo-nitoring of bovine respiratory multocida pasteurellosis.

OBJECTIVE To systematically evaluate the efficacy and safety of vonoprazan in the treatment of gastroesophageal reflux disease， and to provide evidence-based reference for clinical drug use. METHODS Randomized controlled trials （RCTs） about vonoprazan （trial group） versus placebo or proton pump inhibitor （control group） were searched in PubMed， the Cochrane Library， Web of Science， CNKI， Wanfang， VIP and CBM databases from the inception to June， 2022. After literature screening and data extraction， the qualities of included literature were evaluated with bias assessment tool recommended by Cochrane system evaluator manual 5.1.0. Meta-analysis， sensitivity analysis and publication bias analysis were conducted by using RevMan 5.4 software. RESULTS A total of 9 RCTs were included， involving 1 882 patients. The results of meta-analysis showed that： total response rate [OR＝1.94，95%CI（1.45，2.58），P＜0.000 01]， cure rate [OR＝2.27，95%CI（1.33，3.86），P＝0.003] and remission rate [OR＝1.81，95%CI（1.28， 2.55）， P＝0.000 7] of trial group were significantly higher than control group； there was no significant difference in the incidence of adverse drug events， diarrhea， nasopharyngitis， upper respiratory tract infection and alkaline phosphatase elevation between two groups （P＞0.05）. The results of subgroup analysis showed that cure rate of trial group was significantly higher than control group at 2 weeks of treatment （P＜0.05）； at 4 and 8 weeks of treatment， there was no significant difference in the cure rate between two groups （P＞0.05）. There was no statistically significant difference in the cure rate between two groups at 2， 4 and 8 weeks of treatment among the patients with Los Angeles grade A/B （P＞0.05）； among the patients with Los Angeles grade C/D， the cure rate of patients in the trial group was significantly higher than control group at 2， 4 and 8 weeks of treatment （P＜0.05）. The results of sensitivity analysis and publication bias analysis showed that the results of this study were robust and the possibility of publication bias was small. CONCLUSIONS Vonoprazan has a considerable effectiveness and safety in the treatment of gastroesophageal reflux disease.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Objective To investigate the effect of personality characteristics on near-term postoperative mental health of patients with laryngeal squamous cell carcinoma (LSCC). Methods We included 119 patients with LSCC who underwent surgical treatment. The recent psychological state was assessed by SCL-90, SAS and SDS 5 to 7 days after surgery. The EPQ was used to evaluate the personality characteristics of patients after operation. Multiple linear stepwise regression method was used to analyze the influencing factors of SAS and SDS scores of LSCC patients. Results The postoperative scores of SCL-90, SAS and SDS of LSCC patients were significantly higher than the Chinese norm (P≤0.05). The scores of P scale and N scale in EPQ were higher than the domestic norm (P < 0.01). The scores of somatization, obsessiveness, anxiety, depression, hostility, phobia, paranoia and psychosis were significantly higher than the Chinese norm (P < 0.05). Family income, surgical method, postoperative radiochemotherapy, psychoticism and neuroticism personalities were the influencing factors of postoperative SAS score (P < 0.01). Family income, surgical method, postoperative radiochemotherapy, neurotic personality were the influencing factors of postoperative SDS score (P < 0.01). Conclusion LSCC patients have near-term depression, anxiety and other psychological disorders after operation. In terms of personality, they have psychoticism and neuroticism. Family income, surgical methods, postoperative radiochemotherapy, psychoticism and neuroticism are independent risk factors affecting postoperative SAS and SDS scores.

Objective:To analyze the clinical characteristics and risk factors of juvenile dermatomyositis (JDM) with relapses by comparing clinical features, treatment and disease course among JDM patients with and without relapses.Methods:A retrospective analysis of 102 JDM patients from Children's Hospital of Nanjing Medical University between March 2017 and March 2021 was carried out. Patients were divided into two groups based on whether a JDM relapse had occurred or not. Initial clinical features, laboratory tests and treatment were compared between the two groups. T-test or Mann-Whitney U test was used for measurement data, chi-square test or fisher exact probability was used for count data. The features associated with risk of relapses were analyzed by multivariate logistic regression. Results:Among 102 children with JDM, twenty patients (19.6%) relapsed during drug reduction or after drug withdrawal. The mean duration to the first relapse was 3.24 years (range: 9 months to 7 years). Myositis specific antibodies (MSA) were positive for 8 (40.0%) patients with relapses. With 5 cases were anti-nuclear matrix protein 2 positive, 2 cases were anti-transcription interme-diary factor 1 gamma positive, 1 case was anti-signal recognition particle (SRP) positive, the other 12 cases were MSA negative. By binary logistic regression analysis, we found that peripheral calcinosis [ OR(95% CI)=17.54(1.55, 198.64), P=0.021], and interstitial lung disease [ OR(95% CI)=3.83(1.27, 11.59), P=0.017] were independently related to JDM with relapses. Fifty-three patients (51.9%) received methylpre-dnisolone pulse therapy for initial treatment and 13 (65.0%) patients with relapses received methylprednisolone pulse for initial treatment. There was no significant difference between the two groups ( χ2=1.70 , P=0.193). Tumor necrosis factor alpha antagonist combined with methotrexate (MTX) had achieved good results in clinical treatment in children with relapses. Conclusion:The risk of relapses is high in children with JDM. Calcinosis and interstitial lung disease at disease onset can predict a relapsing disease course. Aggressive treatment is urgently demanded for patients with JDM, especially those with relapses.

The dysfunction of T cells, especially the interaction of antigen presenting cells and CD4 + T cells, leads to abnormal activation of CD4 + T cells and the initiation of adaptive immune response.Dysfunction of the immune system plays an important role in the pathogenesis of rheumatoid arthritis.It is always considered as the central link of synovial continuous inflammation, articular cartilage and bone destruction in rheumatoid arthritis patients.Exploring CD4 + T cell differentiation and cell subsets provides a new perspective for understanding of arthritis and helps to identify new drug targets.

Objective To investigate the efficacy and safety of tocilizumab inpatients with refractory systemic'onset juvenile idiopathic arthritis (SoJIA),and to provide a new option for the treatment of this severe disease.Methods We retrospectively studied 25 cases of hospitalized patients with refractory SoJIA treated withtocilizumab,of whom 22 had data that fit for analysis,from May 2005 to February 2016.Data of 22 cases were collected retrospectively from physicians in charge of the patients.Children with SoJIA were treated with nonsteroidal antiinflammatory drugs (NSAIDs),Glucocorticoid (GC),methotrexate,cyclosporin A,etanerceptetc before,but still in high disease activity due to inadequate response were involved.Weretrospective analyzedthe laboratory test results like C'reactive protein (CRP),Erythrocyte sedimentation rate (ESR),Ferritin and other inflammatory index.Improvement of pain,fever,rash,hepatosplenomegaly and lymphadenectasis of active SoJIA (disease course ≥6 months,and inadequate response to NSAIDs and GC) after tocilizumab treatment (Body weight ≥30 kg,8 mg/kg;Body weight＜30 kg,12 mg/kg,per 4 weeks) were analyzed.Safety data of 22 cases were collected throughout the treatment period including neutropenia,infections,anaphylaxis and elevated liver enzymes etc.We also retrospectively analyzedthe dose change of GC and the long'term effect.Dichtomous paramenters were compared teween groups using thex2 test.Continuous parameters were compared using the analysis of uariance.Results In comparison to the indices before the treatment,the level of CRP [(8.7±2.2) mg/L vs (111.6±74.4) mg/L,F=5.192,P=0.002],ESR [(6.4±6.3) mm/1 h) vs (65.6±24.3) mm/1 h,F=50.393,P=0.000],white blood cell (WBC) [(8.4±2.5)×109/L vs (17.6±8.6)×109/L,F=9.321,P=0.000],Neutrophil count [(4.9±2.4)×109/L vs.(14.4±8.7)×109/L,F=10.541,P=0.000],blood platelet (PLT) [(269.5±79.2)×109/L vs (405.4± 145.3)×109/L,F=5.704,P=0.000] and globulin [(19.2±4.1) g/L vs (30.1±3.8) g/L,F=22.896,P=0.000] decreased rapidly and hemoglobin [(118.3±9.0) g/L vs (108.5±9.8) g/L,F=4.693,P=0.002] increased significantly at 24 weeks after Tocilizumab (TCZ) treatment.Clinical manifestationssuch as fever,rash,hepatosplenomegaly,joint swelling and pain were significantly improved.GC dose [(1.25±3.8) mg·kg-1·d-1 vs (16.2±12.8) mg·kg-1·d-1,F=8.21,P=0.000] were significantly reduced after TCZ treatment (P＜0.05);American College of Rheumatology (ACR) Pedi 30/50/70/90 was improved after TCZ treatment.Adverse events occurred in 3 cases of 25 children,who were not included in the statistical analysis group.Conclusion This retrospective case series has demonstrated the efficacy of tocilizumab in SoJIA,low incidence of adverse reactions.Further studies are needed to be developed because this case series haslimited sample size.

Objective To investigate the clinical features and long - term prognosis of neonatal lupus erythe-matosus(NLE)and to improve the understanding of NLE. Methods The clinical manifestations and related serologi-cal tests of NLE children diagnosed from June 2010 to January 2014 were analyzed. Regular follow - up was carried out to detect the general condition,rash,blood routine,urine routine,liver and kidney function,complement,red blood cell sedimentation rate(ESR),auto antibodies,electrocardiogram,and ultrasound cardiogram. Results Among the 11 NLE cases,there were 6 male and 5 female patients. All had lesions on skin,3 cases had hematologic changes,7 cases were had liver damage,and 4 cases had heart impairment. The antinuclear antibody and anti - sjogren sydrome A/ Ro antigen (SSA/ Ro)were positive in all the patients. The anti - sjogren sydrome B antigen was positive in 5 patients. The anti -double stands deoxyribonucleic acid antibody was positive in 4 patients. Antibody against U1 - ribonudeoprotein was positive in 3 patients,and the level of ESR was higher in 5 patients. The antinuclear antibody and anti - SSA/ Ro anti-body were positive in all mothers. Only 1 mother had no symptom before pregnancy,7 patients had SLE,3 patients had sjogren syndrome. Seven patients received protect liver enzyme treatment,3 cases of glucocorticoid therapy,and 1 case had combined intravenous treatment with gamma globulin. Among the 11 cases,10 cases were followed up for 10 months to 4 years,while 1 case died from complete bundle branch block after 5 weeks of birth. At 1 year old,10 cases of cuta-neous lupus damage had liver damage were resorted to normal,and the rheumatic autoimmune related autoantibodies of 9 cases turned to be negative,but 1 case was diagnosed as Kawasaki disease when she was 1 year old. Conclusions One of the most common clinical manifestations of NLE was damage of skin,had the liver and blood system abnormity were common but usually not serious. Heart disease especially complete atrioventricular block was less. The long - term follow - up for children with NLE is necessary,and the majority of the prognosis is good,as only a few have the possibi-lity of developing other autoimmune diseases.

OBJECTIVETo evaluate the renal function in treatment-naive patients with hepatitis B virus (HBV) related cirrhosis and to identify the risk factors for renal impairment.

METHODSWe collected the data of 860 HBV-related cirrhosis patients hospitalized in our unit between Jan 1, 2011 and Dec 31, 2011. Liver function of the patients was assessed with Child-Pugh score system, and the renal function with estimated glomerular filtration rate (eGFR) calculated by Modification of Diet in Renal Disease (MDRD) equation recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI). We investigated the prevalence of renal impairment (eGFR>60 ml/min/1.73 m(2)) among these patients and explored the risk factors for renal impairment.

RESULTSOf the 860 patients, 296 had complete clinical data and were included in our analysis. The overall incidence of renal impairment among the enrolled patients was 8.45% (25/296). Patients with Child-Pugh stage C showed a significantly higher incidence of renal impairment than those with stages B and A (17.17% [17/99] vs 6.67%[7/105] vs 1.09% [1/92], P<0.001). Age, history of hyperuricemia, and Child-Pugh score were identified as the risk factors for renal impairment in these patients.

CONCLUSIONIn patients with HBV-related liver cirrhosis, the incidence of renal impairment increases significantly with deterioration of the liver function, and renal function should be regularly monitored in these patients for appropriate antiviral treatment.

Adult ; Female ; Glomerular Filtration Rate ; Hepatitis B virus ; Hepatitis B, Chronic ; physiopathology ; Humans ; Incidence ; Kidney ; physiopathology ; Liver Cirrhosis ; physiopathology ; virology ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors